We have investigated the antiviral activity of the photoactivatable compound gilvocarcin (GV) an antitumor agent which is closely related to psoralen. GV binds to DNA in the presence of near UV radiation (UVA, 320-400nm) through cycloaddition, blocks DNA replication, and causes DNA strand breaks. GV was considered to be an ideal treatment for the inactivation of viruses which contaminate transfusable blood products, since viral nucleic acid would be targeted, thereby eliminating most damage to platelets and red blood cells which are anucleate. GV has been shown to be toxic to bacterial and mammalian cells at picomolar levels in the presence of UVA radiation. We evaluated the effectiveness of GV for photoinactivation of several viruses, including the bacterial viruses phi X174, T7, PRD1 and phi 6, and herpes simplex virus, type 1 (HSV). Some inactivation of the bacterial viruses was observed with UVA radiation alone (exposures <26 kj/m2). Photosensitized inactivation was observed only with phi 6 and T7 at 2 uM GV. HSV was photosensitive at 10 3-fold lower concentrations of GV (1 nM). For both HSV and T7, the survival curves displayed multicomponent kinetics, indicating that 80- 90% of these viruses constituted sensitive populations (D37 for T7 = 4.0 kj/m2 at 2 uM; D37 for HSV < 1 kj/m2 at 1nM. Neither the strandedness or type of viral nucleic acid, nor the presence of lipid components, was solely responsible for this wide range of sensitivities. These date were presented at the annual meeting of the American Society for Photobiology in San Antonio, TX, June, 1991 an a manuscript is in preparation.